Ayca Tas

Endocan, a novel marker of endothelial dysfunction in patients with essential hypertension: comparative effects of amlodipine and valsartan

Abstract Vascular inflammation plays an important role in the pathophysiology of hypertension and high levels of endocan may reflect ongoing vascular inflammation in hypertensive patients. In the present hypothesis-generating study, we aimed at investigating the comparative effects of amlodipine and valsartan on endocan levels in newly diagnosed hypertensive patients. The study population consisted of 37 untreated hypertensive patients who were randomized to the two treatment arms. After baseline assessment, each patient was randomly allocated to either 10 mg daily of amlodipine (n = 18, 7 males) or 160 mg daily of valsartan (n = 19, 3 males) and treated for a 3-month period. Sphygmomanometric blood pressure (BP) and serum endocan were measured before and every 2 weeks during drug treatment. There was no statistically significant difference between the two treatment arms as far as baseline socio-demographic and clinical characteristics are concerned. After a 3-month treatment period, systolic and diastolic BP values significantly reduced by antihypertensive treatment (p < 0.001). Furthermore, endocan levels were significantly decreased in both treatment arms (p < 0.05). However, amlodipine caused a greater percent decrease in circulating endocan levels compared with valsartan at the end of the treatment period. Both drugs reduced high sensitivity C-reactive protein values. However, the statistical significant difference vs baseline was achieved only in the group treated with amlodipine. No correlation was found between endocan plasma levels and BP reduction. The results of this hypothesis-generating study suggest that amlodipine and valsartan decrease endocan levels in newly diagnosed hypertensive patients. The effects, which are more evident with amlodipine, may contribute to the anti-inflammatory effects exerted by the two drugs on the vascular target.

Is there a relation between Murine double minute 2 T309G polymorphism and lung cancer risk in the Turkish population

Abstract Introduction: Association between Murine double minute 2 T309G polymorphism and lung cancer risk has been investigated in several populations, but results of these studies are inconsistent. We aimed to investigate the effect of Murine double minute 2 T309G polymorphism on development of lung cancer in a Turkish population. Methods: Total 200 subjects including 100 patients and 100 controls were analyzed and used polymerase chain reaction and restriction fragment length polymorphism methods for genotyping analysis of the polymorphism. Results: We found that smokers compared with non-smokers have approximately eight fold higher lung cancer risk [p=0.0001, OR=8.27 (4.02–16.9)]. Frequency of GG genotype was higher in patients than in controls, but this ratio was not significant (χ2=3.5, p=0.17). Genotype distribution of the polymorphism was not different neither patients with non-small cell lung cancer nor patients with small cell lung cancer (χ2=2.89, p=0.57). We analyzed together with demographic feature (except smoking habit), clinicopathological findings and genotype frequencies of this polymorphism, and any association with lung cancer risk was not obtained. Conclusion: No correlation between Murine double minute 2 T309G polymorphism and lung cancer risk was detected in this Turkish population. Özet Giriş: Çeşitli popülasyonlarda akciğer kanseri riski ile Murine double minute 2 T309G polimorfizminin birlikteliği incelenmiş, fakat bu çalışmaların sonuçları arasında tutarsızlık olduğu görülmüştür. Bu çalışmada, bir Türk popülasyonunda akciğer kanserinin gelişimi üzerine Murine double minute 2 polimorfizminin etkisini araştırmayı amaçlanmıştır. Yöntemler: Bu çalışmada, 100 hasta 100 kontrolden oluşan toplam 200 örnek incelenmiş ve bu polimorfizmin genotip analizi için polimeraz zincir reaksiyonu ve restriksiyon fragment uzunluk polimorfizmi yöntemleri kullanılmıştır. Bulgular: Çalışmada sigara içmeyenlerle karşılaştırıldığında sigara içenlerin yaklaşık olarak sekiz kat daha fazla akciğer kanseri gelişme riskine sahip oldukları bulunmuştur [p=0.0001, OR=8.27 (4.02–16.9)]. GG genotipi kontrollere oranla hastalar arasında daha yüksek oranda bulunmuştur fakat bu oran anlamlı değildir (χ2=3.5, p=0.17). Bu polimorfizmin genotip dağılımı ne küçük hücreli akciğer kanseri olan hastalarda ne de küçük hücreli olmayan akciğer kanseri olan hastalarda farklılık göstermediği bulunmuştur (χ2=2.89, p=0.57). Polimorfizmin genotip sıklıkları, klinikopatolojik bulgular ve demografik özellikler (sigara alışkanlığı hariç) birlikte değerlendirilmiş ve bu bulgular arasında akciğer kanseri riski ile herhangi bir ilişki elde edilememiştir. Sonuç: Bu Türk popülasyonunda akciğer kanseri riski ve Murine double minute 2 T309G polimorfizmi arasında bir korelasyon belirlenememiştir.

Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats

A total of 66 male Wistar rats were used and six groups (control: 10 animals and experimental: 12 animals) were formed. While a separate control group was established for each study period, mad honey application to the animals in the experimental group was carried out with a single dose (12.5 g kg−1 body weight (b.w.); acute stage), at a dose of 7.5 g kg−1 b.w. for 21 days (subacute stage), and at a dose of 5 g kg−1 b.w. for 60 days (chronic stage). Tissue and blood oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), 4-hydroxynonenal (HNE), superoxide dismutase, catalase, glutathione (GSH) peroxidase, and glucose-6-phosphate dehydrogenase), hepatic chemical metabolizing parameters in the liver (cytochrome P450 2E1, nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase, nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase (CYTC), GSH S-transferase (GST), and GSH), and micronucleus and comet test in some samples were examined. Findings from the study showed that single and repeated doses given over the period increased MDA, NO, and HNE levels while decreasing/increasing tissue and blood antioxidant enzyme activities. From hepatic chemical metabolizing parameters, GST activity increased in the subacute and chronic stages and CYTC activity increased in the acute period, whereas GSH level decreased in the subacute stage. Changes in tail and head intensities were found in most of the comet results. Mad honey caused oxidative stresses for each exposure period and made some significant changes on the comet test in certain periods for some samples obtained. In other words, according to the available research results obtained, careless consumption of mad honey for different medical purposes is not appropriate.

Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

Background: Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have been reported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutations in p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphism on breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an association between MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population. Materials and Methods: We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reaction and restriction length fragment polymorphism methods were used. Results: A significant difference was observed between case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). There was a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37). However, we did not find any relationships among tumor grade and metastasis status and this polymorphism. Conclusion: This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be risk factors for breast cancer in our Turkish population.

Superoxide Dismutase 1 (SOD 1) A251G Polymorphism

Abstract Objective: A genetic polymorphism of SOD1 A251G(rs2070424) is in the 3rd intron region of the SOD gene. The aim of this study was to determine the frequencies of the polymorphisms of the SOD1 A251G in a Turkish population, including 494 healthy individuals. Methods: The 494 Turkish individuals were genotyped for polymorphisms of SOD1 gene. The distribution of SOD1 A251G polymorphisms in this population was examined using a PCR-RFLP method. Genotype and allele frequencies were estimated by counting. Hardy–Weinberg equation between expected and observed genotype distributions was assessed using the X2 test. Results: In the present study, the distribution of SOD1 A251G polymorphisms in a Turkish population including 494 (females: 278, 56.3% and males: 216, 43.7%) healthy individuals was examined. The mean age of the study population was 38.4±16.6 years (males, 39.8±17.1; females, 37.3±16.1). The observed genotype frequencies of SOD1 A251G were 86.2, 13.4 and 0.4% for AA, AG and GG, respectively. Conclusions: This study provides basic information about the allele and genotype frequency distributions of polymorphisms in the SOD1 A251G gene studied. These frequencies may be useful parameters as a reference for future studies on genetic basis of various diseases and cancer susceptibility.

Investigation of the association between the MDM2 T309G polymorphism and gastric cancer

Murine double minute clone 2 oncoprotein (MDM2) is a key component in the regulation of the tumour suppressor p53. The association between the MDM2 polymorphism and gastric cancer (GC) has been investigated in Turkish population. In the present case-control study, the aim was to investigate the association between genetic polymorphisms of the MDM2 gene (a major regulator of p53 function) and primary GC risk in a Turkish population. The polymorphism, T309G (rs2279744) in the MDM2 gene was determined in patients with GC (n=65) and in healthy control subjects (n=67) using the polymerase chain reaction-restriction fragment length polymorphism method. The findings were evaluated using logistic regression and χ2 tests. No statistically significant differences were observed between the control subjects and patients with GC regarding smoking status. A comparison between GC cases and control subjects indicated a statistically significant difference for family history of cancer [odds ratio (OR)=0.17; 95% confidence interval (CI), 0.05-0.56; χ2=0.19; P=0.01]. A significant difference was identified in the GG genotype distribution between GC patients and control subjects (OR=4.58; 95% CI, 1.18-17.79; P=0.022). Thus, the results of the present study indicate that the MDM2 gene T309G intron (GG) genotype may be an important risk factor for GC development in the Turkish population.

Manganese-superoxide dismutase (MnSOD) polymorphisms/ Manganez-süperoksit dismutaz (MnSOD) polimorfizmi

Abstract Objective: Manganese superoxide dismutase (MnSOD,SOD2), the only known superoxide scavenger in mitochondria, may be particularly important for antioxidant defense because mitochondria are the major sites for cellular metabolism and hence production of reactive oxygen species. Methods: In this study, 440 Turkish individuals were genotyped for polymorphisms of SOD2 gene. The distribution of these polymorphisms in this population was examined using a PCRRFLP method. Results: In the present study, a total of 440(females: 201, 46% and males: 239, 54%) healthy individuals were studied. The mean age of the study population was 54,41±5,76 years (males, 55,34±5,76; females, 53,12±7,16). The observed genotype frequencies of SOD2 were 17.5, 50.5 and 32.0% for CC, CT and TT, respectively. Conclusion: This study provides basic information about the allele and genotype frequency distributions of polymorphisms of rs4880 in the SOD2 gene studied. These frequencies may be useful parameters as a reference for future studies on genetic basis of various diseases and cancer susceptibility. Özet Amaç: Mangan süperoksit dismutaz (MnSOD, SOD2) hücresel metabolizmada reaktif oksijen türlerinin en çok oluştuğu mitokondride bilinen tek süperoksit süpürücü ve antioksidan savunma siteminin önemli bir enzimidir. Metod: Bu çalışmada, toplam 440 Türk sağlıklı bireyler incelendi. Türk toplumunda bu polimorfizmin dağılımı bir PCR-RFLP yöntemi kullanılarak incelenmiştir. Bulgular: Bu çalışmada, toplam 440 (kadın: 201,%46 ve erkek: 239, %54) Türk sağlıklı bireyler incelendi. Çalışma grubunun yaş ortalaması 54,41±5,76 yıl (erkek, 55,34±5,76; kadın, 53,12±7,16) idi. Mangan süperoksit dismutaz gözlenen genotip frekansları sırasıyla CC: %17,5 CT: %50,5 ve TT için %32,0 olarak tespit edildi. Sonuç: Bu çalışma, Türk toplumunda SOD2 geninde rs4880 polimorfizmlerinin allel ve genotip frekans dağılımları hakkında temel bilgiler sağlamıştır. Bu frekanslar gelecekte çeşitli hastalıklar ve kanser yatkınlığı çalışmalarında yararlı referans parametreler olabilir.